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Predicting Bird Flu's Future

Recombinomics founder Henry Niman, says he has two papers ready for publication -- as soon as he solves a mystery involving Korean pigs.

Courtesy of Henry L. Niman

Avian flu could be morphing into forms going unobserved by most researchers, if one scientist's theory is correct.

On one hand, it would be bad news to discover that scientists don't have much of a handle on the flu's mutation activities. But it could also be good news: If Henry Niman's theory is correct, it would mean that scientists can predict avian flu's future iterations. And that would be handy for engineering vaccines that will work a year or two after they're manufactured.

Niman has founded a biotech company called Recombinomics based on his theory that avian flu genes are swapping pieces in a predictable way. This gene reorganization is called recombination, something that scientists agree happens during certain biological events, but not in the flu virus. They believe instead that viruses swap whole genes only, a process called re-assortment.

"Recombination has a lot of ramifications," Niman said. "You can begin to be able to make a vaccine for something that hasn't emerged yet. You can also predict how bad things can be."

Almost any other flu scientist, however, will say while it's possible to track virus history, there's no reliable way to predict its future mutations.

Now Niman says the conventional wisdom is wrong. With a database detailing genetic sequences, bird migration patterns, and the age and geography of patients, among other information, scientists could indeed make estimates as to how, when and where the virus will change. That is if they accepted his theory of recombination, but that doesn't seem likely until Niman can offer solid proof.

"Normally in the influenza virus, because it has a segmented genome, new variants are created by re-assortment and not by recombination," said Dr. Erich Hoffmann, scientific manager at St. Jude Children's Research Hospital in Memphis, Tennessee. Hoffman is part of a team that has identified a gene involved in the transformation of the influenza virus. The National Institutes of Health is using the discovery to develop next season's flu vaccine.

"There are some very, very rare examples proven where one has to postulate that it’s recombination," he said. One case occured in British Columbia during a flu outbreak in last year, another happened in Chile.

These are examples of what's called "non-homologous" recombination, which means two different genes are combining to create a new gene in a virus. Niman agrees it's a rare phenomenon. But he believes "homologous" recombination is happening more often in bird flu. Homologous recombination involves just one gene and two viruses. For example, if a cell is infected by both avian flu and human flu, a gene in either the avian or human virus could take on parts of the other.

The avian flu that has led to the death of more than 100 million birds and at least 42 humans – about three-quarters of those infected – is known as H5N1. It contains eight genes, and the fear is that it will reassemble, swapping one of its bird-infecting genes for a human-infecting gene. Scientists predict that could be the beginning of a pandemic that could kill millions of people, rivaling the 1918 epidemic that killed 40 million people.

Niman says the fear should be redirected. If the virus takes on a human gene, the immune system might recognize the infection and mount an immune response. But with recombination, he said, the virus evolves to contain a gene that is part avian and part human. That would allow it to both infect humans and retain its high mortality rate. Niman calls it "elegant evolution."

"Some of the recombination is by trial and error, but (the virus is) also trying things that have worked in the past," he said. "It happens all the time – I have a paper showing that's how the 1918 pandemic strain was formed. Until it's published, the CDC will say it's not recombination."

Indeed, very few researchers will discuss whether recombination is even a possibility in avian flu. In science, a common motto is "publish or perish." Scientists are (rightfully) a skeptical bunch. They won't embrace a new idea like Niman's until it's published in a peer-reviewed journal – a scientific publication that sends research papers out to various experts for comments and approval before it will print the study.

"Without this kind of quality control it's very difficult to find meaningful results and make conclusions," Hoffman said. "It's not a perfect system, but it's better than just spreading information (without) quality control."

Niman has two papers ready to submit, but he is waiting for key information about some pigs in South Korea that he says could clinch his case for recombination.

Niman says gene sequences of the flu infecting the pigs – posted in October 2004 to GenBank, a public gene database – contain genes that are part human and part avian.

"Anybody looking at the sequence would come to the conclusion that it's recombination," Niman said.

Most worrisome is that the human segment of the flu appears to be derived from a 1933 virus related to the one that caused the 1918 flu pandemic. Most human immune systems would have no defense against it, because it was man-made in a London lab in 1940.

But now, the World Health Organization and the South Korean government say the sequence may have been caused by a lab error. Niman is waiting for three independent labs to verify the pig samples before he submits his research to a peer-reviewed journal.

"I'm trying to get the Korean story nailed down," he said. "There are still other examples. But that will be the one to finish it off. You can't get it any better than that."